Category
- PI3K/Akt/mTOR
- Epigenetics
- Methylation
- Immunology & Inflammation
- Protein Tyrosine Kinase
- Angiogenesis
- Apoptosis
- Autophagy
- ER stress & UPR
- JAK/STAT
- MAPK
- Cytoskeletal Signaling
- Cell Cycle
- TGF-beta/Smad
- DNA Damage
- Stem Cells & Wnt
- Ubiquitin
- Neuronal Signaling
- NF-κB
- GPCR & G Protein
- Endocrinology & Hormones
- Transmembrane Transporters
- Metabolism
- Proteases
- Microbiology
- Others
Archives
ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias
Leukemias, including acute myeloblastic leukemias, acute lymphoblastic lekemias (ALL), chronic myelogenous leukemia (CML), demonstrate significantly increased expression of Wilms tumor gene 1 protein (WT1), a zinc finger transcription factor. However, this potential therapeutic target is undruggable. Dubrovsky et al. developed an antibody, ESKM, which is therapeutically effective on acute and chronic leukemias in murine models. The article was published on Blood.
WT1 is an intracellular transcription factor, therefore, it is hard to be directly inhibited by small-molecule drugs or antibody therapies. Researchers established a human IgG1 T-cell receptor mimic (TCRm) monoclonal antibody called ESKM, which targets a 9-amino acid sequence of WT1, expressed in the context of cell surface HLA-A*02. They found ESKM is effective and not affected by gatekeeper resistance T315I. T315I is a mutation that inactivates tyrosine kinase inhibitors (TKIs), which is a common uncurative therapy of Philadelphia chromosome-positive (Ph+) ALL. However, TKIs combined with ESKM is capable to cure mice Ph+ ALL. In addition, ESKM is specific to the leukemia cells, so it perform minimal effects to other cells. The findings suggested ESKM a promising nontoxic drug for PH+ leukemias.
Reference:
Blood. 2014 May 22;123(21):3296-304.
Related Products
| Cat.No. | Product Name | Information | Publications | Customer Product Validation |
|---|---|---|---|---|
| S1026 | Imatinib Mesylate (STI571) | Imatinib Mesylate (STI571) is an orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively. | (54) | (6) |
| S2475 | Imatinib (STI571) | Imatinib (STI571) is a multi-target inhibitor of tyrosine kinase with inhibition for v-Abl, c-Kit and PDGFR, IC50 values are 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively. | (84) | (6) |
| S1021 | Dasatinib | Dasatinib is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM in cell-free assays, respectively. | (158) | (13) |
| S1490 | Ponatinib (AP24534) | Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. | (63) | (6) |
| S8030 | Plerixafor (AMD3100) | Plerixafor (AMD3100) is a chemokine receptor antagonist for CXCR4 and CXCL12-mediated chemotaxis with IC50 of 44 nM and 5.7 nM in cell-free assays, respectively. | (23) | (4) |
